肢端肥大症的医学治疗目前是通过使用第一代生长抑素受体配体(fgSRLs)作为一线药物的试错方法进行的。有效率约为50%,和后续药物通过临床判断。一些生物标志物可以预测fgSRLs反应。在这里,我们报告了ACROFAST研究的结果,一项临床试验,其中评估了基于fgSRLs预测生物标志物的方案.
方法:前瞻性试验(21所大学医院),比较了12个月内两种治疗方案的有效性和控制时间:A)个性化方案,其中首选fgSRLs作为单一疗法或与pegvisomant或,pegvisomant作为单一疗法,取决于短急性奥曲肽试验(sAOT)结果,肿瘤T2磁共振(MRI)信号或E-钙黏着蛋白的免疫染色,B)对照组,其治疗总是通过fgSRL开始,并且在证明控制不充分之后包括其他药物。
结果:85名患者参与;个性化组45名,对照组40名。与对照组相比,个性化方案中更多的患者实现了激素控制(78%vs53%,p<0.05)。生存分析显示,根据年龄和性别调整,实现激素控制的风险比为2.53(CI1.30-4.80)。来自个性化手臂的患者在较短的时间内得到控制(p=0.01)。
结论:个性化医疗使用相对简单的方案是可行的,并且允许更多的患者在更短的时间内实现控制。
Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated.
METHODS: prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control.
RESULTS: Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01).
CONCLUSIONS: Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.